单/双指数模型DWI评估裸鼠肺腺癌移植瘤早期化疗疗效的对比研究

Diffusion-weighted imaging for monitoring the early response of lung adenocarcinoma xenograft in nude mouse to chemotherapy:a comparative study of monoexponential and biexponential models

目的:探讨单、双指数模型DWI评估裸鼠肺腺癌移植瘤早期化疗疗效的可行性和准确性,并筛选最佳参数。方法:在48只雌性裸鼠中建立肺腺癌移植瘤模型,并将其随机分为治疗组A及对照组B,A组和B组分别采用腹腔内注射顺铂和生理盐水。每组各随机抽取4只裸鼠(AM组、BM组)于4个时间点(第0、3、7和10天)行体素内不相干运动成像(IVIM-DWI),测量病灶的体积及表观扩散系数(ADC)、真实扩散系数(D)、灌注分数(f)和灌注相关扩散系数(D*)。两组各16只裸鼠(AP、BP组)分别在对应的4个时间点每次随机抽取4只进行病理学检查。比较各组不同时间点肿瘤体积和DWI参数值,并采用受试者工作特征曲线(ROC)分析各参数值的诊断效能。结果:化疗第3、7、10天AM组肿瘤的ADC和D值较BM组明显升高,f值明显降低(P<0.05)。化疗第10天AM组肿瘤体积较BM组明显缩小(P<0.05),而第3、7天肿瘤体积的差异无统计学意义(P>0.05)。治疗第3天各参数的ROC下面积依次是0.917(D)、0.833(ADC)和0.667(f);以D值>1.02×10-3 mm2/s作为阈值,敏感度和特异度分别为83.3%和100%;以ADC值>1.08×10-3 mm2/s作为阈值,敏感度和特异度分别为66.7%和100%。病理检查显示,在化疗第3、7和10天时AP组肿瘤细胞坏死和出血较BP组明显增多,AP组微血管密度(MVD)及细胞增殖抗原67(Ki67)的表达水平随时间延长而下降,AP组与BP组间MVD及Ki67表达水平分别在第7、10天及第3、7、10天时差异有统计学意义(P<0.05)。结论:肺腺癌移植瘤化疗后D、ADC和f值的改变早于肿瘤体积的变化;D值对肺腺癌早期化疗疗效的评价可能优于ADC值。

Objective：To study the feasibility and accuracy of mono-exponential and bi-exponential models DWI for e- valuating the curative effect of chemotherapy on lung adenocarcinoma xenograft in nude mice, and to select the optimal quan- titative parameters. Methods： Transplantation tumor model of human lung adenocarcinoma was established in 48 female EALB/c nude mice, and the nude mice were randomly divided into two groups. In group A, cisplatin was administered by in- traperitoneal injection, meanwhile the equivalent sterile saline was administered in group B. Four mice were selected random- ly from group A and four in group B （named as AM and BM group） ,and IVIM-DWI scanning was performed immediately at baseline,3th,7th and 10th day,the DWI parameters including ADC,D,f and D＊ values and tumor volume were calculated. The rest of the 32 mice were randomly divided into Ap and Bp group （n=16 for each） ,4 mice were selected randomly from Ap and Bp group respectively to undergo pathology examination in different observation time. The changes of tumor volume and DWI parameters of different groups were compared at every time points. The receiver operating characteristic curve （ROC） was applied to significant parameters to compare the area under the curve and calculate their sensitivity and specifi- city. Results：The ADC and D values of tumor in AM group were significantly higher while f value was significantly lower than those in BM group at the 3th,Tth and 10th day after chemotherapy （all P〈0.05）. In AM group,the tumor volume was significantly decreased than those of BM group at the 10th day （P〈0.05）. The area under curve was 0. 917 for D,0. 833 for ADC, 0. 667 for f value at the 3th day after treatment. When D value〉1. 02 × 10-3 mm2/s, ADC value〉 1.08 × 10-3 mm2/s, the corresponding sensitivity and specificity were 83.3 % and 100%, 66.7 % and 100% ,respectively. In Ap group the tumor necrosis and hemorrhage were significantly increased than those in Be group at the 3th, 7th and 10th day, In Ap groups, MVD value decreased and was significantly lower than those of Bp groups at the 7th and 10th day,while Ki67 at the 3th, 7th and 10th day （P〈（0.05）. Conclusion：D,ADC and f value of subcutaneous transplantation tumor model of lung adenocarci- noma changed earlier than tumor volume after chemotherapy of lung cancer. The D value derived from biexponential may besuperior to the ADC from monoexponential model in evaluating the efficacy of chemotherapy in nude mice.